Combined radionuclide-chemotherapy and in vivo imaging of hepatocellular carcinoma cells after transfection of a triple-gene construct, NIS, HSV1-sr39tk, and EGFP

You La Lee, Yong Jin Lee, Sohn Joo Ahn, Tae Hyun Choi, Byung Seok Moon, Gi Jeong Cheon, Sang Woo Lee, Byeong Cheol Ahn, Jeoung Hee Ha, Jaetae Lee

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The sodium iodine symporter (NIS) or mutant Herpes-simplex virus type1 sr39 thymidine kinase (HSV1-sr39tk) gene is used for in vivo imaging and cancer therapy. Transfection of both NIS and HSV1-sr39tk genes to hepatocellular carcinoma cells (Huh-7/NTG) could enhance intracellular accumulation of therapeutic radionuclides and guanosine nucleoside analogue prodrugs to produce better outcomes than single gene therapy. Non-invasive imaging with I-124, F-18 FHBG and combination therapy with I-131 and GCV were performed in hepatocellular carcinoma cells transfected with NIS, HSV1-sr39tk and GFP. Our results show that: (1) all three genes are stably expressed in Huh-7/NTG cells, (2) I-125 and H3-PCV uptake were markedly increased in the Huh-7/NTG cells in vitro, (3) cellular survival and tumor growth of Huh-7/NTG was inhibited by I-131 or GCV both in vitro and in vivo, and was much prominent with combination therapy, (4) in vivo imaging with I-124 and F-18 FHBG revealed increased uptake in the Huh-7/NTG tumor. Our results demonstrated the potential of combination gene therapy using NIS and HSV1-sr39tk followed by radioiodine treatment and chemotherapy in human hepatocellular carcinoma cells.

Original languageEnglish
Pages (from-to)129-138
Number of pages10
JournalCancer Letters
Volume290
Issue number1
DOIs
StatePublished - 1 Apr 2010

Keywords

  • EGFP
  • Human sodium iodide symporter
  • I-124
  • Mutant herpes-simplex virus type1 sr39 thymidine kinase
  • Triple-reporter gene

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